This invention relates to particulate antimicrobial agents capable of killing intracellular microorganisms, and to the administration of these agents to patients in an effective manner.
Advances in medicinal chemistry have primarily been accomplished by the synthesis of new compounds which demonstrated improved efficacy and/or reduced toxicity because of their chemical structure. While these types of innovations continue unabated, a major objective of pharmaceutical research today involves the targetting of drugs to specific organs or tissues to maximize efficacy and minimize adverse side effects.
Despite the availability of a variety of antimicrobials, many infections continue to cause significant morbidity and mortality among patients. Several reasons can be cited to explain this phenomenon. All antimicrobials, including those exhibiting so-called broad-spectrum activity, are only effective against a finite number of organisms. In addition, bacteria are capable of developing resistance to an antibiotic by acquisition of plasmids or chromosomal mutation. These changes in the bacteria may allow for alteration of the antimicrobial agent by enzyme production or block antimicrobial agent transport into the bacteria. In addition, a bacterial strain can develop an alternative metabolic pathway or different peptide linkage and become totally resistant to a particular antibiotic. Prophylactic use of antibiotics is now generally avoided to reduce the incidence of strain specific resistance of many common bacteria.
Most organisms are susceptible to killing by the phagocytic cells. However, some microbes, so called facultative and obligate intracellular parasites, are incompletely killed by these cells. No totally effective treatment for infections by these organisms is commercially available today.
Currently administered drugs are almost exclusively water-soluble compounds with demonstrated efficacy for a particular disease or condition. Aqueous solubility of a drug permits rapid and uniform mixing with blood for delivery to the infection site; however, this phenomenon also results in drug delivery to other organs where deleterious side effects can and often do occur. In addition, high aqueous solubility often prevents a drug from entering cells which inherently limits effective treatment for numerous maladies. Surmounting these problems is a major challenge to pharmaceutical manufacturers today. Many approaches are currently being investigated and may be viable in the future. This invention, the use of particulate pharmaceuticals as antimicrobial agents, is a novel approach which shows promise for imminent clinical application.